title: Inflammatory cytokines induce the expression of basic fibroblast growth factor (bFGF) isoforms required for the growth of Kaposi's sarcoma and endothelial cells through the activation of AP-1 response elements in the bFGF promoter.
abstract: BACKGROUND
  The growth of Kaposi's sarcoma (KS) spindle cells is dependent on a number of inflammatory cytokines as well as the autocrine growth factor, basic fibroblast growth factor (bFGF). Moreover, inflammatory cytokines, found at increased levels in KS lesions, promote bFGF production in KS and endothelial cells.
  
  
  OBJECTIVE
  To determine the induction of bFGF isoforms, role of bFGF in cell growth and activation of the bFGF promoter by inflammatory cytokines.
  
  
  METHODS
  3H-Thymidine uptake, bFGF immunoblotting and transfection of dominant-negative MAP kinase components were used to study the effect of cytokines on the bFGF promoter, bFGF isoform expression and proliferation of KS cells.
  
  
  RESULTS
  Treatment with oncostatin M (OSM), interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha induced the expression of 18, 22 and 24 kDa bFGF isoforms in KS and human umbilical vein endothelial cells (HUVEC). Antisense bFGF oligonucleotides interfered in the induction of KS cell proliferation by individual cytokines. OSM, IL-1 and TNF-alpha induced the transcriptional activation of a bFGF promoter reporter gene in parallel with the activation of an AP-1 reporter. Dominant-negative ERK and dominant-negative JNK mutants interfered in cytokine-induced activation of these reporters in accordance with the role of the MAP kinase cascades in individual cytokine signaling pathways.
  
  
  CONCLUSIONS
  OSM, IL-1 and TNF-alpha induce KS cell growth by inducing the expression of various bFGF isoforms. Moreover, bFGF production by KS and HUVEC is dependent on the activation of the ERK and JNK cascades, which result in the transcriptional activation of the bFGF promoter.
authors.affiliation: Department of Medicine, Jonsson Cancer Center UCLA School of Medicine, Los Angeles, California 90095, USA.
authors.forename: M
authors.initials: M
authors.lastname: Faris
authors.forename: B
authors.initials: B
authors.lastname: Ensoli
authors.forename: N
authors.initials: N
authors.lastname: Kokot
authors.forename: A E
authors.initials: AE
authors.lastname: Nel
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology; D007536:Isomerism; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012514:Sarcoma, Kaposi / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; C508351:OSM protein, human; D016376:Oligonucleotides, Antisense; D010455:Peptides; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D053683:Oncostatin M; D008156:Luciferases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases